She is also known for playing Ana Lucia Cortez on Lost, as well as Leticia "Letty" Ortiz in The Fast and the Furious franchise. She also had a main role in Avatar, which has become the highest-grossing movie ever and her most successful film to date.

When Rodriguez was added to the cast of Resident Evil, the film script was altered by Paul W.S. Anderson. The character Rain, either created entirely for Rodriguez or heavily adapted, caused friction between Anderson and actress Milla Jovovich, who felt her character had been robbed of several action scenes.[1]

She returned to the Resident Evil franchise in its Retribution instalment, playing three separate characters, all of whom being clones of her Rain character from the first film.